Intracellular Calcium and Myocardial Contractility

Abstract

The function of the sarcoplasmic reticulum of the failing myocardiums was studied in vitro by comparing calcium uptake and calcium-activated ATPase in microsomes prepared from hearts of control calves and calves in which right ventricular failure developed during experimentally induced pulmonary hypertension. The rate of calcium uptake averaged .147 µmole·mg -1 ·min -1 at 25°C in the presence of oxalate in control preparations and was significantly reduced in preparations from failing right ventricles (avg .086 µmoles·mg -1 ·min -1 ). Calcium-activated ATPase was also diminished significantly in failure (avg .184 compared to .073 µmoles·mg -1 ·min -1 ). Although two preparations also showed diminished calcium activities in the nonfailing left ventricle, group these activities were not significantly depressed in preparations from ventricle in calves with failure. A similar reduction in calcium activities observed at 37°C with preparations further purified by sucrose gradient centrifugation. The uptake capacity of microsomes, measured as calcium uptake in the absence of oxalate, was not diminished in the preparations from failing hearts. Mitochondrial contamination did not appear to be a factor since azide inhibited calcium activity almost completely in mitochondria, whereas inhibition was less than 10% in microsomes of both control and failing hearts. Ouabain had no effect on the microsomes from failing hearts. These studies indicate that there is a defect in calcium transport in microsomes and a functional abnormality of the sarcoplasmic reticulum in the intact myocardial cell in heart failure which could lead to changes in the excitation-contraction coupling mechanisms of clinical importance.